chr15-98913324-G-A

Variant names:

• chr15-98913324-G-A
• rs951715
• NM_000875.5:c.1828+42G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000875.5(IGF1R):​c.1828+42G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 1,486,490 control chromosomes in the GnomAD database, including 304,719 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.64 (31317 hom., cov: 34)
  • Exomes 𝑓: 0.64 (273402 hom.)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92
• Publications: 20 publications found

Genes affected

IGF1R (HGNC:5465): (insulin like growth factor 1 receptor) This receptor binds insulin-like growth factor with a high affinity. It has tyrosine kinase activity. The insulin-like growth factor I receptor plays a critical role in transformation events. Cleavage of the precursor generates alpha and beta subunits. It is highly overexpressed in most malignant tissues where it functions as an anti-apoptotic agent by enhancing cell survival. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2014]

IGF1R Gene-Disease associations (from GenCC):

• growth delay due to insulin-like growth factor I resistance

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1R	NM_000875.5	c.1828+42G>A		intron_variant	Intron 8 of 20	ENST00000650285.1	NP_000866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF1R	ENST00000650285.1	c.1828+42G>A		intron_variant	Intron 8 of 20		NM_000875.5	ENSP00000497069.1

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97321 AN: 152064 Hom.: 31276 Cov.: 34

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.661

GnomAD2 exomes AF: 0.636 AC: 159641 AN: 250942 AF XY: 0.643

Gnomad AFR exome AF: 0.650

Gnomad AMR exome AF: 0.587

Gnomad ASJ exome AF: 0.656

Gnomad EAS exome AF: 0.494

Gnomad FIN exome AF: 0.658

Gnomad NFE exome AF: 0.638

Gnomad OTH exome AF: 0.652

GnomAD4 exome AF: 0.640 AC: 853579 AN: 1334306 Hom.: 273402 Cov.: 20 AF XY: 0.643 AC XY: 431534 AN XY: 670868

African (AFR) AF: 0.656 AC: 20307 AN: 30946

American (AMR) AF: 0.589 AC: 26235 AN: 44568

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 16607 AN: 25314

East Asian (EAS) AF: 0.550 AC: 21536 AN: 39140

South Asian (SAS) AF: 0.737 AC: 61577 AN: 83590

European-Finnish (FIN) AF: 0.654 AC: 34804 AN: 53184

Middle Eastern (MID) AF: 0.711 AC: 3579 AN: 5032

European-Non Finnish (NFE) AF: 0.635 AC: 632347 AN: 996334

Other (OTH) AF: 0.651 AC: 36587 AN: 56198

GnomAD4 genome AF: 0.640 AC: 97419 AN: 152184 Hom.: 31317 Cov.: 34 AF XY: 0.640 AC XY: 47611 AN XY: 74422

African (AFR) AF: 0.654 AC: 27157 AN: 41510

American (AMR) AF: 0.604 AC: 9235 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2247 AN: 3472

East Asian (EAS) AF: 0.508 AC: 2630 AN: 5180

South Asian (SAS) AF: 0.730 AC: 3524 AN: 4826

European-Finnish (FIN) AF: 0.652 AC: 6907 AN: 10590

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.639 AC: 43471 AN: 67998

Other (OTH) AF: 0.665 AC: 1407 AN: 2116

Alfa AF: 0.621 Hom.: 8362

Bravo AF: 0.637

Asia WGS AF: 0.674 AC: 2342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.0030
DANN	Benign	0.49
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs951715; hg19: chr15-99456553; COSMIC: COSV51272679; COSMIC: COSV51272679;